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Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease
Sameer Bansilal1, Marc P Bonaca2, Jan H Cornel3
1Zena and Michael Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Insights
Patients with prior myocardial infarction and multivessel coronary disease benefit from ticagrelor, experiencing reduced risks of major adverse cardiovascular events and coronary events. Long-term ticagrelor therapy is effective for this high-risk group, though it increases bleeding risk.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) face a high risk of recurrent cardiovascular events.
- The PEGASUS-TIMI 54 trial investigated ticagrelor's efficacy in preventing such events.
Purpose of the Study:
- To evaluate the efficacy and safety of ticagrelor compared to placebo in patients with MVD following a prior MI.
- To assess the impact of ticagrelor on major adverse cardiovascular events (MACE) and coronary events in this specific patient subgroup.
Main Methods:
- A pre-specified analysis of the PEGASUS-TIMI 54 trial stratified patients with prior MI based on the presence of MVD.
- Evaluated the effects of ticagrelor (60 mg and 90 mg) on composite outcomes of cardiovascular death, MI, stroke, coronary death, stent thrombosis, and bleeding events over a median of 33 months.
Main Results:
- Patients with MVD had a higher risk of MACE and coronary events compared to those without MVD.
- Ticagrelor significantly reduced the risk of MACE (HR: 0.82) and coronary events (HR: 0.76) in patients with MVD.
- Ticagrelor increased the risk of TIMI major bleeding (HR: 2.67) but not intracranial hemorrhage or fatal bleeding.
Conclusions:
- Long-term ticagrelor treatment provides substantial relative and absolute risk reductions for MACE and coronary events in patients with prior MI and MVD.
- While ticagrelor increases the risk of major bleeding, it remains an effective option for long-term antiplatelet therapy in this high-risk population.
Background:
Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events.
Objectives:
The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial.
Methods:
Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months.
Results:
A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds.
Conclusions:
Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
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